Protocol/serial number

Study information

Scientific title

Acronym

CIBIS-ELD

Study hypothesis

With bisoprolol, the target dose can be reached more frequently in heart failure patient than with carvedilol.

Please note that as of 15/01/2008 some changes have been made to this trial record. All changes can be seen in the relevant sections of the record, under the date 15/01/2008. Please also note that the anticipated end date of this trial has been extended to 30/06/2008. The previous end date of this was 30/10/2007.

Ethics approval

Ethics approval received from:1. Germany: Ethikkommission der Charité on the 13th June 2007 (Amendment 5) (ref: 125/2004)2. Serbia: Ethics board of the University Hospital on the 31st March 2006 (ref: 6108/18)3. Slovenia: The national medical ethics committee on the 2nd July 2007 (ref: KME 188/06/07)

Trial type

Patient information sheet

Condition

Intervention

Dosages of study drugs: The target dose for bisoprolol was set at 10 mg/d, for carvedilol at 25 mg twice daily (b.i.d.) and 50 mg b.i.d. for patients greater than 85 kg.

Up-titration: The beta-blocker dose is increased to the target dose at fortnightly intervals. Dose titration differs according to the previous medication schedule of each patient. After the initial dose, therapy is commenced with either dose increment 1 or 2. Patients greater than 85 kg receive dose increment 5 after six or eight weeks. This increment indicates an increase in dosage in the carvedilol group only; in the bisoprolol group the increment is only technically treated like a dose increase for blinding purposes. The highest tolerated dose increment is maintained until the primary endpoint is reached (final visit in week 10 or 12). In instances of medication intolerance, patients are instructed not to reduce the dose without medical advice. The physician determines whether the intolerance is avoidable by changing the concomitant medication. If this not the case, the dose is reduced by one increment. A further up-titration is not attempted to minimise the risk of non-adherence by repeatedly provoking symptoms of intolerance. If up-titration is delayed (e.g. by adjusting concomitant medication) but the dose not reduced, it is desirable to attempt reaching the bisoprolol 10 mg target dose during subsequent treatment, even if it was not attained during the study treatment phase. After the 12-week therapy phase, the beta-blocker is not to be abruptly discontinued due to the exacerbation of sympathetic activity. Instead, a beta-blocker should be prescribed as standard treatment after study completion.

Intervention type

Drug

Phase

Not Specified

Drug names

Bisoprolol, carvedilol

Primary outcome measures

Current primary outcome measures as of 15/01/2008:Tolerance (yes/no) of the study medication target dose as per cardiology guidelines. Tolerance (= yes) is defined when:1. Dose titration was possible up to the target dose2. The study medication dose was not reduced. It is irrelevant whether unscheduled T-visits took place if the titration aim was not affected3. The target dose is to be taken at the time of last visit. This dose has remained stable for at least 10 days. Tolerance is ascertained (i.e. there is no reason for dose reduction and the patient did not reduce it independently either)

Previous primary outcome measures:Tolerability, measured as individually achieved dose at end of titration.

Secondary outcome measures

Current secondary outcome measures as of 15/01/2008:Correlation between the medication and the following secondary endpoints:1. Time to treatment failure (TTF) 2. Dose increment attained (% of maximum) for long term treatment3. Number of adverse events (AE) or serious adverse events (SAE) in total as well as itemised according to their relation to dose reduction/ discontinuation of treatment4. Lung function (vital capacity [VC], forced expiratory volume in the first second [FEV1], peak expiratory flow [PEF] and maximal mid-expiratory flow [MEF50]) 5. NYHA class6. 6-minute walk test7. Diastolic function (according to the American Society of Echocardiography [ASE]) and left ventricular function (fractional shortening and EF according to Simpson [looking at four chambers] from echocardiography before and after beta-blocker titration)8. Quality of life, depression and physical well-being (measured with the following instruments: 36-item short form health survey [SF-36], Patient Health Questionnaire [PHQ-D] and KWB-16)9. Heart rate at rest and under stress10. Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and BNP concentration 11. Alteration of total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides plasma concentration12. Investigation of parameters for the current medical treatment of HF patients = 65 years old:13. Frequency of beta-blocker, diuretic, angiotensin converting enzyme (ACE)-inhibitor or angiotensin receptor antagonist prescription 14. Qualitative and quantitative survey of other therapeutic actions 15. Hospitalisations16. Days alive and days out of hospital

Overall trial start date

01/03/2005

Overall trial end date

30/06/2008

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 15/01/2008:1. Age greater than or equal to 65 years2. Current diagnosis of chronic heart failure from New York Heart Association (NYHA) II - IV or ejection fraction (EF) less than 40%3. Clinically stable heart failure for 2 weeks before inclusion4. Informed consent